Identification of a Direct-Acting Antiviral Agent Targeting RNA Helicase via a Graphene Oxide Nanobiosensor

Jungho Kim, Se Jin Park, Jisang Park, Hojeong Shin, Yong Suk Jang, Jae Sung Woo, Dal Hee Min

Research output: Contribution to journalArticlepeer-review

Abstract

Dengue virus (DENV), an arbovirus transmitted by mosquitoes, causes infectious diseases such as dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. Despite the dangers posed by DENV, there are no approved antiviral drugs for treatment of DENV infection. Considering the potential for a global dengue outbreak, rapid development of antiviral agents against DENV infections is crucial as a preemptive measure; thus, the selection of apparent drug targets, such as the viral enzymes involved in the viral life cycle, is recommended. Helicase, a potential drug target in DENV, is a crucial viral enzyme that unwinds double-stranded viral RNA, releasing single-stranded RNA genomes during viral replication. Therefore, an inhibitor of helicase activity could serve as a direct-acting antiviral agent. Here, we introduce an RNA helicase assay based on graphene oxide, which enables fluorescence-based analysis of RNA substrate-specific helicase enzyme activity. This assay demonstrated high reliability and ability for high-throughput screening, identifying a new helicase inhibitor candidate, micafungin (MCFG), from an FDA-approved drug library. As a direct-acting antiviral agent targeting RNA helicase, MCFG inhibits DENV proliferation in cells and an animal model. Notably, in vivo, MCFG treatment reduced viremia, inflammatory cytokine levels, and viral loads in several tissues and improved survival rates by up to 40% in a lethal mouse model. Therefore, we suggest MCFG as a potential direct-acting antiviral drug candidate.

Original languageEnglish
Pages (from-to)25715-25726
Number of pages12
JournalACS Applied Materials and Interfaces
Volume13
Issue number22
DOIs
Publication statusPublished - 2021 Jun 9

Keywords

  • antiviral agent
  • biosensor
  • dengue virus
  • graphene oxide
  • high-throughput drug screening

ASJC Scopus subject areas

  • Materials Science(all)

Fingerprint

Dive into the research topics of 'Identification of a Direct-Acting Antiviral Agent Targeting RNA Helicase via a Graphene Oxide Nanobiosensor'. Together they form a unique fingerprint.

Cite this